comparison of cytochrome P450 inhibitory and dopaminergic activity of Piperine, Curcumin and Capsaicin.

Psychiatric disorders are a heterogeneous group of mental disorders that manifest as abnormal mental or behavioral habits that cause the individual discomfort or disability. Dopamine imbalance plays a major role in many psychiatric disorders. Piperine, Curcumin and Capsaicin are CYP P450 3A4 & 2D6 inhibitors. The objective of this study is to determine the dopaminergic activity of Piperine, Curcumin and Capsaicin and also to compare cytochrome P450 3A4 and 2D6 inhibition activity by methods. In this study, we utilised compounds such as Piperine, Curcumin and Capsaicin were subjected to Lipinski's rule of five, and ligands were also evaluated for toxicity profile and ADMET properties. Furthermore, the ligands were performed in docking studies. All three compounds were docked with three different targeted proteins (PDB IDs: 4D7D, 4WNW and 6LUQ). According to the docking result, Piperine has higher binding energy(-8.55 kcal/mol)(-8.1 kcal/mol)(-8.57 kcal/mol) when compared with Curcumin(-7.39 kcal/mol)(-5.61 kcal/mol)(-6.57 kcal/mol) and Capsaicin (-6.86 kcal/mol)(-6.57 kcal/mol)(-5.42 kcal/mol) and also with standard drug (-8.61 kcal/mol)(-7.65 kcal/mol)(-6.16 kcal/mol). The present study concluded that the bioactive compound Piperine has a better inhibitory activity of CYP 3A4, 2D6 enzymes and dopamine D2 receptor among the three compounds and also with the standard drug thioridazine.